Cancer is a class of diseases that can affect people of all ages. Accordingly, there is considerable effort to provide therapies that can treat or diagnose cancer in patients. Targeted delivery of nanocarriers in the body has been discussed recently as a potential new avenue in drug delivery and diagnostic imaging techniques. Unfortunately, obstacles still exist in making nanocarrier based-products that can effectively treat or diagnose cancer.
Many if not all solid tumors either express matrix metalloproteinase (MMP) enzymes on their surface or excrete it into the surrounding matrix or cause MMP enzymes to be produced via angiogenesis (see, Y. Chau, F. E. Tan, and R. Langer, Bioconjugate Chem, 2004, 15:931-941 and A. Matter, ‘Tumor Angiogenesis as a Therapeutic Target’, DRUG DISCOVERY TODAY, 6:1005-1024 (2001)). Thus, the tumor environment is particularly rich in MMP 2, 9, and 13 enzyme content as well as others, such as members of the membrane bound family, MMP 14-17. The activity of MMP enzymes in a mouse tumor model has been exquisitely revealed by use of a FRET-based MMP enzyme assay where fluorescent dye is released in vivo once the dye-bearing molecule is transported into the tumor (L. Zhu, J. Xie, M. Swierczewska, F. Zhang, Q. Quan, Y. Ma, X. Fang, K. Kim, S. Lee, X. Chen, Theranostics, 2011, 1:18-27).
Nanoparticles, such as liposomes, are commonly modified to incorporate polyethylene glycol (PEG) groups on their surface to enhance in vivo performance. It would be advantageous to target the liposomal nanoparticle to a tumor cell related receptor or enzyme within the tumor and also have it targeted for cellular uptake of the cytotoxic payload (or other cargo) by endocytosis (or other internalization mechanism) driven by enzyme/receptor recognition and binding events.
There remains a need for new targeted delivery approaches that can treat or diagnose cancer and provide ways to facilitate personalized care for a patient. The present disclosure addresses this need.